ArticleThe Journal of biological chemistry2009
Role of ADAMs in the ectodomain shedding and conformational conversion of the prion protein.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 137 citations in OpenAlex.
- Cellular prion protein and its derived peptides: multifaceted roles in neurodegenerative diseases and potential as biomarkers.Cell & bioscience · 2026Review
- Therapeutic Trajectories in Human Prion Diseases.Sub-cellular biochemistry · 2025Review
- Prion Protein Endoproteolysis: Cleavage Sites, Mechanisms and Connections to Prion Disease.Journal of neurochemistry · 2025Review
- Prion protein alters viral control and enhances pathology after perinatal cytomegalovirus infection.Nature communications · 2024Article
- Cleavage site-directed antibodies reveal the prion protein in humans is shed by ADAM10 at Y226 and associates with misfolded protein deposits in neurodegenerative diseases.Acta neuropathologica · 2024Article
- Application of N-Terminal Labeling Methods Provide Novel Insights into Endoproteolysis of the Prion ProteinACS chemical neuroscience · 2024Article
- A methodology to globally assess ectodomain shedding using soluble fractions from the mouse brain.Frontiers in psychiatry · 2024Article
- New implications for prion diseases therapy and prophylaxis.Frontiers in molecular neuroscience · 2024Review
- Inducing prion protein shedding as a neuroprotective and regenerative approach in pathological conditions of the brain: from theory to facts.Neural regeneration research · 2023Review
- An LRP1-binding motif in cellular prion protein replicates cell-signaling activities of the full-length protein.JCI insight · 2023Article
- Anchorless risk or released benefit? An updated view on the ADAM10-mediated shedding of the prion protein.Cell and tissue research · 2023Review
- Beta-endoproteolysis of the cellular prion protein by dipeptidyl peptidase-4 and fibroblast activation protein.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Human prion diseases and the prion protein - what is the current state of knowledge?Translational neuroscience · 2023Review
- The LRP1/CD91 ligands, tissue-type plasminogen activator, αScientific reports · 2022Article
- Prion Protein: The Molecule of Many Forms and Faces.International journal of molecular sciences · 2022Review
- A Soluble PrPJournal of immunology (Baltimore, Md. : 1950) · 2022Article
- Endoproteolysis of cellular prion protein by plasmin hinders propagation of prions.Frontiers in molecular neuroscience · 2022Article
- Ligands binding to the prion protein induce its proteolytic release with therapeutic potential in neurodegenerative proteinopathies.Science advances · 2021Article
- Neuroprotective effect and potential of cellular prion protein and its cleavage products for treatment of neurodegenerative disorders part I. a literature review.Expert review of neurotherapeutics · 2021Review
- Neuroprotective effect and potential of cellular prion protein and its cleavage products for treatment of neurodegenerative disorders part II: strategies for therapeutics development.Expert review of neurotherapeutics · 2021Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 4 countries.
Funding
Abstract
The cellular prion protein (PrP(C)) is essential for the pathogenesis and transmission of prion diseases. PrP(C) is bound to the plasma membrane via a glycosylphosphatidylinositol anchor, although a secreted, soluble form has also been identified. Previously we reported that PrP(C) is subject to ectodomain shedding from the membrane by zinc metalloproteinases with a similar inhibition profile to those involved in shedding the amyloid precursor protein. Here we have used gain-of-function (overexpression) and loss-of-function (small interfering RNA knockdown) experiments in cells to identify the ADAMs (a disintegrin and metalloproteinases) involved in the ectodomain shedding of PrP(C). These experiments revealed that ADAM9 and ADAM10, but not ADAM17, are involved in the shedding of PrP(C) and that ADAM9 exerts its effect on PrP(C) shedding via ADAM10. Using dominant negative, catalytically inactive mutants, we show that the catalytic activity of ADAM9 is required for its effect on ADAM10. Mass spectrometric analysis revealed that ADAM10, but not ADAM9, cleaved PrP between Gly(228) and Arg(229), three residues away from the site of glycosylphosphatidylinositol anchor attachment. The shedding of another membrane protein, the amyloid precursor protein beta-secretase BACE1, by ADAM9 is also mediated via ADAM10. Furthermore, we show that pharmacological inhibition of PrP(C) shedding or activation of both PrP(C) and PrP(Sc) shedding by ADAM10 overexpression in scrapie-infected neuroblastoma N2a cells does not alter the formation of proteinase K-resistant PrP(Sc). Collectively, these data indicate that although PrP(C) can be shed through the action of ADAM family members, modulation of PrP(C) or PrP(Sc) ectodomain shedding does not regulate prion conversion.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.